HIST1H4F基因甲基化在三阴性乳腺癌中的预后价值

doi:10.3969/j.issn.1009-976X.2024.01.008

摘要/Abstract

摘要： 目的探讨HIST1H4F基因甲基化在三阴性乳腺癌中的意义。方法收集31例乳腺癌新鲜的癌组织标本及正常乳腺组织标本,提取DNA后使用亚硫酸盐进行甲基化转化处理,荧光定量 PCR进行HIST1H4F基因甲基化检测,分析癌组织标本和正常乳腺组织中的HIST1H4F基因甲基化差异情况,并分析三阴性乳腺癌的HIST1H4F基因甲基化情况。同时收集37例三阴性乳腺癌的石蜡标本,提取DNA后同样方法处理再进行HIST1H4F基因甲基化检测,分析HIST1H4F基因甲基化与三阴性乳腺癌预后的关系。结果新鲜组织标本中周围正常乳腺组织和癌组织中HIST1H4F甲基化阳性率均为74.2%（23/31）,两者的HIST1H4F甲基化阳性率无明显区别（χ²=0000,P=1.000）,分析发现三阴性乳腺癌组织中HIST1H4F甲基化阳性率高于非三阴性乳腺癌（93.8% vs. 53.3%,P=0.015）,HIST1H4F甲基化阳性乳腺癌的组织学分级Ⅲ级和ER阴性的乳腺癌中比率高于HIST1H4F甲基化阴性乳腺癌（60.9% vs. 12.5%,P=0.037;69.6% vs. 25.0%,P=0.043）。在三阴性乳腺癌的石蜡组织标本进行HIST1H4F甲基化检测,发现HIST1H4F甲基化阳性率为27.0%,且HIST1H4F甲基化阳性组和阴性组的DFS（50.0% vs. 66.7%,χ²=1.141,P=0.285）和OS（90.0% vs. 96.3%,χ²=1.635,P=0.201）在统计学上均无明显区别。结论在新鲜组织标本中三阴性乳腺癌中检测HIST1H4F基因甲基化阳性率高,HIST1H4F基因甲基化阳性乳腺癌的组织学Ⅲ级和ER阴性比率高,而在三阴乳腺癌石蜡组织标本中检测的HIST1H4F甲基化阳性率较低,尚不能确定HIST1H4F甲基化与三阴性乳腺癌预后是否相关,仍有待于进一步研究。

关键词: 乳腺癌, HIST1H4F, 甲基化

Abstract: Objective To investigate prognostic value of HIST1H4F gene methylation in triple-negative breast cancer. Methods Thirty-one fresh breast cancer tissue samples and normal breast tissue samples were collected. After DNA extraction, bisulfite was used for methylation transformation. Fluorescence quantitative PCR was used to detect the methylation of HIST1H4F gene, and the difference of HIST1H4F gene methylation in cancer tissue samples and normal breast tissue was analyzed. The relationship between methylation of HIST1H4F gene and prognosis of triple-negative breast cancer was analyzed.At the same time, paraffin specimens of 37 cases of triple-negative breast cancer were collected, DNA was extracted and processed by the same method, and HIST1H4F gene methylation was detected to analyze the relationship between HIST1H4F gene methylation and prognosis of triple-negative breast cancer. Results The HIST1H4F methylation positive rates were 74.2% （23/31） in both normal and cancer tissues, and there was no significant difference between the two groups （χ²=0.000, P=1.000）. the HIST1H4F methylation positive rate in triple-negative breast cancer was higher than that in non-triple-negative breast cancer （93.8% vs. 53.3%, P=0.015）, HIST1H4F methylation-positive group had higher HIST1H4F grade Ⅲ and ER negative ratio than HIST1H4F methylation-negative group （60.9% vs. 12.5%, P=0.037; 69.6% vs. 25.0%, P=0.043）. For HIST1H4F methylation in paraffin tissue specimens of triple-negative breast cancer and found a HIST1H4F methylation positive rate of 27.0%,there was no significant difference between HIST1H4F methylation positive and negative groups in DFS （50.0% vs. 66.7%, χ²=1.141, P=0.285） and OS （90.0% vs. 96.3%, χ²=1.635, P=0.201）. Conclusion The positive rate of HIST1H4F gene methylation in triple negative breast cancer is high in fresh tissue samples, and histological grade Ⅲ and ER negative ratios were high in HIST1H4F gene methylation-positive breast cancer. While HIST1H4F methylation positive rate was low in paraffin tissue samples of triple-negative breast cancer. Whether HIST1H4F methylation is associated with triple-negative breast cancer prognosis remains to be determined and further studies are needed.

Key words: breast cancer, HIST1H4F, methylation

中图分类号:

R739.7

严珊珊, 雷雯, 李帅杰, 王永南. HIST1H4F基因甲基化在三阴性乳腺癌中的预后价值[J]. 岭南现代临床外科, 2024, 24(01): 54-58.

YAN Shan-shan, LEI Wen, LI Shuai-jie, WANG Yong-nan. Prognostic value of HIST1H4F gene methylation in triple-negative breast cancer[J]. Lingnan Modern Clinics In Surgery, 2024, 24(01): 54-58.

参考文献

[1] Muse ME, Titus AJ, Salas LA, et al.Enrichment of CpG island shore region hypermethylation in epigenetic breast field cancerization[J]. Epigenetics, 2020, 15(10): 1093-1106.
[2] Li J, Zhou X, Li L, et al.The association between CTSZ methylation in peripheral blood and breast cancer in Chinese women[J]. Front Oncol, 2023, 13: 1148635.
[3] Napieralski R, Schricker G, Auer G, et al.PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients[J]. Breast Care (Basel), 2021, 16(5): 523-531.
[4] Buschbeck M, Hake SB.Variants of core histones and their roles in cell fate decisions, development and cancer[J]. Nat Rev Mol Cell Biol, 2017, 18(5): 299-314.
[5] Amatori S, Tavolaro S, Gambardella S, et al.The dark side of histones: genomic organization and role of oncohistones in cancer[J]. Clin Epigenetics, 2021, 13(1): 71.
[6] Dong S, Li W, Wang L, et al.Histone-Related Genes Are Hypermethylated in Lung Cancer and Hypermethylated HIST1H4F Could Serve as a Pan-Cancer Biomarker[J]. Cancer Res, 2019, 79(24): 6101-6112.
[7] Mielnicki LM, Asch HL, Asch BB.Genes, chromatin, and breast cancer: an epigenetic tale[J]. J Mammary Gland Biol Neoplasia, 2001, 6(2): 169-182.
[8] Holmes WF, Braastad CD, Mitra P, et al.Coordinate control and selective expression of the full complement of replication-dependent histone H4 genes in normal and cancer cells[J]. J Biol Chem, 2005, 280(45): 37400-37407.
[9] Varol N, Keles İ, Yildiz H, et al.Methylation analysis of histone 4-related gene HIST1H4F and its effect on gene expression in bladder cancer[J]. Gene, 2023, 866: 147352.
[10] Sandoval J, Mendez-Gonzalez J, Nadal E, et al.A prognostic DNA methylation signature for stage I non-small-cell lung cancer[J]. J Clin Oncol, 2013, 31(32): 4140-4147.
[11] Wang X, Liu S, Xue Y.Clinicopathological features and prognosis of male breast cancer[J]. J Int Med Res. 2021, 49(10): 3000605211049977.
[12] Liang Q, Ma D, Gao RF, et al.Effect of Ki-67 Expression Levels and Histological Grade on Breast Cancer Early Relapse in Patients with Different Immunohistochemical-based Subtypes[J]. Sci Rep. 2020, 10(1): 7648.
[13] De-la-Cruz-Ku G, Luyo M, Morante Z, et al. Triple-negative breast cancer in Peru: 2000 patients and 15 years of experience[J]. PLoS One, 2020, 15(8): e0237811.
[14] Tan H, Fu D.Influence of advanced age on the prognosis of triple-negative breast cancer patients: A surveillance, epidemiology, and end results-based study[J]. J Cancer Res Ther, 2023, 19(Supplement): S0.
[15] Zhou D, Li M, Xu F, Zheng Q, et al.The prognostic significance of skin involvement in breast cancer patients with chest wall recurrence[J]. Ann Med, 2023, 55(1): 2232299.